Congenital CMV (CCMV) is the most common congenital infection occurring in 0.5% -1.0% of all live born infants in the U.S. It is estimated tat between 25% and 40% of all childhood hearing loss is caused by intrauterine CMV infection. Most infants (~90%) with congenital CMV infection have no detectable clinical abnormalities at birth (asymptomatic infection), and about 10% of these children develop SNHL. Nearly half of children with CMV-associated SNHL have normal hearing at birth and develop hearing deficits during critical stages of language development. The pathogenesis of CCMV-related SNHL is poorly understood and there is currently no established therapy for all patients with CCMV infection. Infection with multiple virus strains occurs but recent data has revealed that the variability of CMV strains within a host equals that of RNA viruses. As children with CCMV harbor large amounts of virus for many years, we hypothesize that diversity is likely generated by high levels of virus replication and higher viral diversity leads to adverse outcome in this infection. The purpose of this proposal is to define the diversity of CMV strains in all compartments of shedding in a large, well defined population of children with congenital CMV infection. We will also examine the effects of factors that alter viral replication; the immune response and antiviral therapy, on changes in viral populations over time. By determining the overall significance of viral diversity in CCMV infection, and further defining how selective pressures affect diversity and subsequent sequelae, we will then be able to define correlates of SNHL and design better anti-virals to improve long term outcomes in infants with CCMV. PUBLIC HEALTH RELEVANCE: Congenital CMV is the most congenital infection in newborns, and a leading cause of hearing loss in children, yet little is understood about how the virus causes disease. This project will define how frequent multiple strains of CMV cause congenital infection and determine if more viral strains are associated with hearing loss. Identifying a correlate for CMV related hearing loss will aid in identifying the 10-15% of infants with congenital CMV at highest risk for adverse outcome and allow for more focused monitoring of hearing and the opportunity to intervene with better therapies during critical stages of speech and language development.